Abstract

Sickle cell anaemia is a manifestation of a single point mutation in haemoglobin, but inflammation and pain are the insignia of this disease which can start in infancy and continue throughout life. Earlier studies showed that mast cell activation contributes to neurogenic inflammation and pain in sickle mice. Morphine is the common analgesic treatment but also remains a major challenge due to the side effects and ability to activate mast cells. Therefore, we examined the cannabinoid receptor-specific mechanisms to ameliorate mast cell activation, neurogenic inflammation and hyperalgesia, using HbSS-BERK sickle and cannabinoid receptor 2 deleted sickle mice. We show that cannabinoids ameliorate mast cell activation, inflammation and neurogenic inflammation in sickle mice via both cannabinoid receptors 1 and 2. Thus, cannabinoids influence systemic and neural mechanisms, ameliorating the disease pathobiology and hyperalgesia in sickle mice. This study provides a “proof of principle” for the potential of cannabinoid/cannabinoid receptor-based therapeutics to treat several manifestations of sickle cell anaemia.